CERVICAL DORSAL RHIZOTOMY ENHANCES SEROTONERGIC INNERVATION OF PHRENIC MOTONEURONS AND SEROTONIN-DEPENDENT LONG-TERM FACILITATION OF RESPIRATORY MOTOR OUTPUT IN RATS

We tested the hypothesis that spinal plasticity elicited by chronic bi lateral cervical dorsal rhizotomy (C-3-C-5; CDR) has functional implic ations for respiratory motor control. Surgery was performed on rats (C DR or sham-operated) 26 d before phrenic motoneurons were retrogradely labeled with cholera toxin. Rats were killed 2 d later, and their spi nal cords were harvested and processed to reveal the cholera toxin-lab eled phrenic motoneurons and serotonin-immunoreactive terminals. The n umber of serotonin-immunoreactive terminals within 5 mu m of labeled p hrenic motoneuron soma and primary dendrites increased 2.1-fold after CDR versus sham-operation. Time-dependent phrenic motor responses to h ypoxia were compared among CDR, sham-operated, and control rats. Anest hetized, paralyzed, vagotomized, and artificially ventilated rats were exposed to three, 5 min episodes of isocapnic hypoxia (Fi(O2) = 0.11) , separated by 5 min hyperoxic intervals (Fi(O2) = 0.5). One hour afte r hypoxia, a long-lasting, serotonin-dependent enhancement of phrenic motor output (long-term facilitation) was observed in both sham and co ntrol rats. After CDR, long-term facilitation was 108 and 163% greater than control and sham responses, respectively. Pretreatment of CDR ra ts with a 5-HT2 receptor antagonist (ketanserin tartrate, 2 mg/kg, i.v .) before episodic hypoxia prevented long-term facilitation and reveal ed a modest (-28 +/- 13%; p < 0.05) long-lasting depression of phrenic motor output. The results indicate that CDR: (1) increases serotonerg ic innervation of the phrenic motor nucleus; and (2) augments serotoni n-dependent long-term facilitation of phrenic motor output. These resu lts further suggest a form of plasticity based on changes in the capac ity for neuromodulation.